Mice expressing HLA-DQ6alpha8beta transgenes develop polychondritis spontaneously

Relapsing polychondritis (RP) is a human autoimmune disease of unknown etiology in which cartilaginous sites are destroyed by cyclic inflammatory episodes beginning, most commonly, during the fourth or fifth decade of life. We have previously described collagen-induced polychondritis that closely mirrors RP occurring in young (6-8 weeks old) HLA-DQ6alphabeta 8alphabeta transgenic Abeta0 mice, following immunization with heterologous type II collagen (CII). We present evidence here that transgenic strains expressing the DQ6alpha8beta transgene develop spontaneous polychondritis (SP) at the mouse equivalent of human middle age (4.5-6 months and 40-50 years old, respectively) and display polyarthritis, auricular chondritis and nasal chondritis--three of the most common sites affected in RP. Auricular chondritis in SP, like RP but unlike CII-induced polychondritis, exhibited a relapsing/remitting phenotype, requiring several inflammatory cycles before the cartilage is destroyed. Elevated serum levels of total IgG corresponded with the onset of disease in SP, as in RP and CII-induced polychondritis. No CII-specific immune response was detected in SP, however--more closely mirroring RP, in which as few as 30% of RP patients have been reported to have CII-specific IgG. CII-induced polychondritis displays a strong CII-specific immune response. SP also demonstrated a strong female preponderance, as some workers have reported in RP but has not observed in CII-induced polychondritis. These characteristics of SP allow for the examination of the immunopathogenesis of polychondritis in the absence of an overwhelming CII-specific immune response and the strong adjuvant-induced immunostimulatory influence in CII-induced polychondritis. This spontaneous model of polychondritis provides a new and unique tool to investigate both the initiatory events as well as the immunopathogenic mechanisms occurring at cartilaginous sites during the cyclic inflammatory assaults of polychondritis.